The primary objective of this research proposal is that of understanding the pathogenesis of growth retardation in nutritional deficiency states. The immediate goals are: 1) to study the effect of nutritional deficiency disease states on growth, growth hormone concentrations, somatomedin activity, and cartilage glycosaminoglycan metabolism and to relate these to microscopic changes and other growth parameters. Studies will attempt to define the role of nutrition in the modulation of plasma somatomedin activity and they may also allow additional understanding into the mechanisms controlling normal growth. To perform these studies, we will study the effects of specific alterations of dietary proteins, fats, and carbohydrates on plasma growth hormone concentrations, somatomedin activity, growth rate, cartilage metabolism, and other growth parameters. 2) We will extend these observations to the study of specific essential amino acid deficiencies, vitamin deficiencies, and mineral deficiencies, as well as studying the effects of varying degrees of nutritional deficiencies and refeeding on growth hormone concentrations, somatomedin activity, cartilage glycosaminoglycans, as well as the effect of growth hormone administration on the above parameters. We will further attempt to correlate these data with microscopic changes to delineate specific mechanisms for growth retardation and nutritional deficiency disease states.